IMI PHARMATRAIN SYLLABUSTHE SYLLABUS FOR PHARMACEUTICAL MEDICINE / DRUG DEVELOPMENT

(V2.0; January 2018)

1.1 Strategy and organisation of research including collaborative approaches e.g. with academia

1.2 Disease models; target identification, validation and selection

1.3 Receptor-based approaches: agonists, antagonists, enzyme inhibitors, genomics, proteomics

1.4Other therapeutic approaches: natural products, drug-coupled devices, advanced therapies

e.g. gene therapy, cell therapies, tissue engineering

1.5 Hit-to-lead, lead optimisation and candidate compound selection for further development

1.6 In silico, in vitro and in vivo testing of new compounds

1.7 Principles of translational medicine

1.8Relationship between animal and human pharmacology, molecular biology and physiology e.g.

biomarkers, functional imaging, modeling and simulation

2.1The elements and functions necessary in the integrated development of a new medicine at a

corporate and international level

2.2 Quality management planning

2.3Project management techniques: drug development plan, project teams, tools and decision-

making from target product profile (TPP) and target product claims (TPC) to registration

2.4Programme-planning in special populations e.g. elderly, children, people with rare diseases,

incapacitated people

2.5 Programmes in developing countries

2.6 R&D portfolio planning including in- and out-licensing of medicines (business development)

2.7 Resource planning: budgeting and cost control

2.8Corporate finance relevant to medicines development: financial control, return on investment,

fixed assets, budgeting, accounting, profitability

3.1Use of in silico, animal- and cell-based models of disease mechanisms to study the

pharmacology of a new drug

3.2Differences in non-clinical safety and toxicity packages between small molecules, biological

medicines, advanced therapies

3.3

The differences and similarities between the pharmacology and toxicology of compounds and

their metabolites in animals, humans and cell preparations that provide qualitative and

quantitative assessment through: genotoxicity, general toxicity, toxicokinetics,

3.4The purpose of descriptive and quantitative in silico, in vitro and in vivo toxicity testing; the

choice of appropriate tests for acute and chronic drug administration

3.5

The common mechanisms of drug-induced organ damage and dysfunction; detection and

elucidation; pathological assessment e.g. structural staining and immune-histochemistry;

functional assessment e.g. QTc interval testing, liver and lung function tests

3.6The scheduling of toxicity tests linked to product development plans, regulatory needs, human

and animal pharmacology, intended clinical use and route(s) of administration

3.7The size, cost and administration of the toxicology programme, its data management, quality

assurance and report writing

3.8

The regular review of toxicology, its inclusion into clinical trial protocols and investigator

brochures, and the appropriate planning and correlation with the clinical evaluation of potential

and observed toxicity in patients

3.9 Safety pharmacology including drug hypersensitivity of both small and large molecules

3.10Toxicokinetics; in vitro and in vivo study of metabolism; administration, distribution,

metabolism, elimination (ADME)

3.11The non-clinical study of biological medicines, vaccines, advanced therapies e.g. gene

therapy, cell therapies, tissue engineering

3.12 The non-clinical study of biopharmaceutical formulations

SECTION 1. Discovery of Medicines

SECTION 2. Development of Medicines: Planning

SECTION 3. Non-Clinical Testing

SECTION 4. Pharmaceutical Development

4.1

Pharmaceutical development of drug substance and drug product, including biological

medicines and advanced therapies: formulations; manufacture and supply of materials;

labelling and presentation; stability and storage; purity; compatibility; disposal

4.2The economic primary production of new compounds and secondary production of research

and market formulations

4.3The choice of formulations depending upon the characteristics of the compound and the

intended uses of the product

4.4

The principles of in vitro and in vivo testing of formulations for bioequivalence, stability,

impurity and incompatibility leading to a final specification, including formulations of follow-on

drugs - generics, biosimilars

4.5Planning clinical trial supply requirements; packaging and labelling of clinical trial supplies;

stability and storage requirements; supply distribution; disposal of remaining stocks

4.6 Clinical trial supplies: preparing matching placebo and competitor products

4.7 Pharmacopoeias: role, use and hierarchy

5.1

Intended therapeutic indications, biomarkers for target engagement, efficacy and safety

requirements, efficacy and safety end-points and criteria for ‘go’ / ‘no-go’ decisions for entry

into humans and progression to Proof of Concept trials

5.2Assessment of non-clinical data and the risk of hazards as prerequisites before administration

to humans

5.3Phase 0 studies: exploratory microdose and sub-therapeutic dose studies; the importance,

limitations and uses of microdoses (ICH M3)

5.4

The early clinical development plan:

exploratory development studies:

- from First in Human to Proof of Concept

- modelling and simulation

- tolerability, metabolism, pharmacokinetics, pharmacodynamics, safety in humans

- safety assessment in patient and healthy volunteer populations

- dose escalating safety committees (membership and role)

- special considerations for advanced therapies and drug-coupled devices

5.5

Pharmacokinetics, ADME, pharmacokinetic / pharmacodynamic models, including concepts of

half-life, volume of distribution, clearance; intrinsic and extrinsic factors which affect the

pharmacokinetics of an innovative medicinal product; dosage and accumulation, bioavailability,

bioequivalence and population pharmacokinetics

5.6 Pharmacogenetics / pharmacogenomics

5.7

Starting dose and dose escalation plan for First in Human and early clinical studies, including

applicability of pharmacokinetics to dosage regimen and study design in First in Human

studies and subsequent Phase II and Phase III clinical trials

5.8First in Human studies: patients and healthy volunteers; principles of Proof of Concept and

dose-finding studies; biomarker qualification / validation for Proof of Concept studies

5.9

Impact of results on planned therapeutic indications, predicted dosage schedules and drug

delivery concepts / formulations; additional animal toxicology requirements; reformulation

studies; new pharmacology studies; risk prediction algorithms to assess safety risks and

enable development of risk management approaches to be applied during continued

development

6.1Options for the clinical development plan (CDP); asset risk assessment and mitigation;

schedules and decision points for the confirmatory clinical development programme

6.2

Translation of the defined target product profile (TPP) into the confirmatory clinical

development programme design; pivotal and other Phase III studies; selection of primary and

secondary endpoints and comparators for Phase III clinical trials; final definition of therapeutic

indications; risk minimisation measures for research participants

6.3

Choice of countries / regions to participate in confirmatory clinical trials; patient numbers and

selection criteria; delivery systems; dosage forms; dosage regimens; clinical trial supplies -

ensuring all these are appropriate for this stage of development

SECTION 6. Confirmatory Development: Strategies

SECTION 5. Exploratory Development (Molecule to Proof-of-Concept)

6.4

Planning and global coordination including alignment of pre-licensing and post-licensing

clinical trial programmes; permitted use of competitor class data, non-clinical data and existing

clinical trial data

6.5 Life-cycle management planning: label extension of therapeutic claims and new formulations

6.6 Obtaining and implementing feedback

7.1

Choice of trial design, considering: non-inferiority / superiority / other design; placebo / other

comparators; patient populations; sample size; locations; randomisation; end-points; statistical

analysis

7.2 New trial designs and required technologies

7.3

Post-authorisation clinical development: Phase IV clinical trials; non-interventional /

observational studies; Real World Evidence (RWE) generation; post-authorisation studies;

patient group registries

7.4 Investigator Brochure: content, review and maintenance

7.5 Protocol development and amendments

7.6Clinical trial feasibility and investigator recruitment; pre-study visits; investigator meetings and

investigator training

7.7 Trial management including investigational site management and site qualification assessment

7.8Contractual arrangements with investigators, academic institutions / hospitals, contract

research organisations, site management organisations; publication rights

7.9 Clinical trial registries

7.10Within-trial decisions e.g. code-breaking, interim analysis, data and safety monitoring

committee (DSMC), premature termination

7.11 Study medication handling and drug accountability

7.12 Adverse event assessment and reporting; emergency cover

7.13 Monitoring and source document verification; evolution of clinical trial monitoring

7.14 Trial master file (TMF)

7.15Quality management system; quality manual; standard operating procedures; quality

assurance and quality control; independent audits; inspections

7.16Reporting of clinical trial data: data sharing and open data, transparency, aggregate clinical

trial report reviews, annual clinical trial reports

7.17Consideration for special populations in clinical trials e.g. elderly, children, extreme ages e.g.

prematures-neonates, incapacitated people; clinical trials in rare diseases

7.18 Medical device and drug-coupled device trials

8.1

Ethics: principles, history including Declaration of Helsinki, Directive 2001/20/EC, ethical

review, informed consent, safety and human dignity of research participants, role of ICH GCP

and other Good Practices (GxPs)

8.2 Ethical issues in biomedical research and pharmaceutical medicine

8.3Protection of research participants; sponsor and investigator responsibilities, in particular, to

avoid conflicts of interest

8.4

Ethical aspects in research questions and study designs for First in Human to post-marketing

and epidemiological studies, including scientific rationale, statistical robustness, appropriate

patient populations, comparators and choice of endpoints; ensuring equipoise in comparator

clinical studies; consideration of conflicts of interest

8.5Ethical aspects of methods of recruitment including database searches and advertising;

participant contact; participant reimbursement

8.6

Informed consent process, including defining benefit-risk balance, requirements for study

participation including for special populations e.g. elderly, children, emergency research,

incapacitated people

8.7Privacy, confidentiality, international standards for data protection and consensual

dissemination of clinical trial data

8.8 Indemnity and insurance for participants, investigators and institutions; complaint procedures

8.9Ethical aspects of clinical trial follow-on: continuation of study medication to study participants,

pre-marketing authorisation, availability pre-reimbursement

SECTION 7. Clinical Trials

SECTION 8. Ethics and Legal Issues

8.10Ethical aspects of trial samples for genomic and related analyses: scientific rationale, ethics

and consequences of anonymisation; biobanks

8.11Ethical aspects of clinical trials in special populations e.g. elderly, children, emergency

research, incapacitated people

8.12Ethical aspects of all stakeholders involved in research of advanced therapies e.g. gene

therapy, cell therapies, tissue engineering

8.13 Ethical aspects of clinical trials in developing countries

8.14 Fraud and misconduct in biomedical research and clinical development

Statistical Aspects of Study Design

9.1Fundamentals: randomisation, choice of endpoints, avoidance of bias, avoidance of

missing data, sample size calculation

9.2 Interim analyses: efficacy, futility, harm

9.3 The design of dose-finding studies

9.4 Equivalence and non-inferiority trials: rationale, choice of margin

9.5Adaptive designs: basic ideas including advantages, concerns, avoidance of

statistical and operational bias

Data Management

9.6 Data collection: options, to include manual and electronic, including diaries

9.7Case report form (CRF) design and completion; source data verification, query

generation and resolution

9.8Data processing: data entry, coding of adverse events, medical history and

concomitant medications; identification of protocol violations and deviations

9.9Databases: maintenance, security, standardisation, streamlining the processes;

Clinical Data Interchange Standards Consortium (CDISC)

Statistical Methods for Analysis

9.10Fundamentals: Null and alternative hypotheses, type I and type II errors, p-values,

confidence intervals, power, analysis sets

9.11

Endpoints: endpoint types (continuous, binary / categorical, time-to-event, rating

scales), data transformation, primary and secondary endpoints, dealing with

multiplicity, evaluating equivalence and non-inferiority

9.12

Specific methodologies: simple statistical tests (parametric and non-parametric),

Odds Ratios, Risk Ratios, Hazard Ratios, Kaplan-Meier curves, modelling to correct

for baseline imbalances and to reduce variation

9.13 Evaluating homogeneity: Forest plots and subgroup evaluation, testing for interaction

9.14 Dealing with missing data through imputation

9.15 Bayesian statistics; basic ideas

9.16Safety data: tables and graphs for the evaluation of adverse events, laboratory data

and other data relating to safety

9.17Diagnosis: sensitivity, specificity and introduction to Receiver Operating

Characteristic (ROC) curves

9.18 Meta-analysis: distinction versus pooling, fixed and random effects models

9.19 Observational studies: matching to minimise bias

The Statistics Process

9.20 Content for the protocol statistical methods section and the Statistical Analysis Plan

9.21Writing the Statistical Study Report and contributing to the Clinical Study Report and

clinical publications; to include the clinical interpretation of statistical analyses

9.22 Critical review of publications

SECTION 9. Data Management and Statistics

10.1Background to and general principles of medicines regulation; evolution of control

mechanisms; differences between agencies

10.2

Philosophy of regulatory oversight; practical input of international bodies e.g. World Health

Organisation (WHO), World Medical Association (WMA), Council for International

Organisations of Medical Sciences (CIOMS), and national agencies

10.3Activities and contribution of International Conference on Harmonisation of Technical

Requirements for Pharmaceuticals for Human Use (ICH)

10.4

Good Practices relevant to medicines development e.g. Good Manufacturing Practice, Good

Laboratory Practice, Good Clinical Practice, Good Clinical Laboratory Practice, Good

Pharmacovigilance Practice

10.5Integration of regulatory affairs into pre- and post-marketing; planning and review of product

strategy

10.6

Regulatory processes in Europe for the evaluation and approval of new medicinal products;

scientific advice; appeal and arbitration procedures; procedures for maintaining, varying and

cancelling European Marketing Authorisations; referrals processes; confidentiality and

transparency

10.7 Regulatory processes: rare diseases, children, advanced therapies

10.8 Regulatory processes: generics and biosimilars

10.9Comparison of international regulatory systems: Europe, US, Japan, and the Rest of the

World; local special regulatory requirements

10.10

European regulations and guidance for Clinical Trial Application (CTA), maintenance and

completion; EU single submission portal; substantial protocol modifications; transparency;

clinical trial regulations in Europe, US, Japan and the Rest of the World

10.11 Common Technical Document (CTD and eCTD); Clinical Overviews; Clinical Summaries

10.12The preparation and submission of marketing applications in major countries e.g. Marketing

Authorisation Application (MAA), New Drug Application (NDA), Japanese NDA, Canadian NDA

10.13Product Information regulation: Summary of Product Characteristics; Package Insert; Patient

Information Leaflets

10.14 Prescription-only and over-the-counter medicines; switches

10.15 Regulatory provisions for the use of unlicensed medicines

10.16 Product restriction, suspension and withdrawal procedures; product defects and recall

10.17 Medical device regulations

10.18Regulation of natural products e.g. herbals, synbiotics, traditional remedies, Chinese

medicines

10.19

Risk management: Risk Management Plan (EU); Risk Evaluation and Mitigation Strategies

(USA); additional monitoring of authorised medicines e.g. inverted black triangle (EU), black

box warning (USA)

10.20Periodic Benefit Risk Evaluation Report (PBRER); Periodic Safety Update Report (PSUR);

Development Safety Update Report (DSUR)

10.21 Regulation and procedures for early access to medicines

10.22 Falsified and counterfeit medicines

10.23Post-authorisation safety studies; post-authorisation efficacy studies; investigator-initiated

studies

11.1 The role of the pharmaceutical professional in drug safety and Pharmacovigilance

11.2

Assessment and classification of Adverse Events, Adverse Drug Reactions, Serious Adverse

Events and Suspected Unexpected Serious Adverse Reactions (SUSARs); evidence for

association and causality

11.3 The concept of benefit-risk balance

11.4 Collection of adverse events in clinical trials

11.5

The role of investigators, clinicians, study monitors, sponsors and manufacturers in the pre-

and post-marketing phases to detect, assess and report adverse events and suspected

adverse drug reactions; regulatory reporting requirements in the pre- and post-marketing

phases; medical literature reports

SECTION 10. Regulatory Affairs

SECTION 11. Drug Safety, Pharmacovigilance and Pharmacoepidemiology

11.6Predisposing factors and the impact of pre-existing disease on the susceptibility for and

severity of adverse events and how to minimise risk

11.7 Post-marketing spontaneous reporting

11.8Reportable events: overdose, medication errors, off-label use, misuse and abuse, experience

during pregnancy

11.9 Drug interactions

11.10 Pharmacoepidemiology

11.11 Main sources of epidemiological pharmacovigilance information

11.12 Signal detection, interpretation and management

11.13 Post-authorisation risk management including issue and crisis management

11.14 Risk communication

12.1Information and disclosure to patients and patient organizations; compliance in patient

engagement activities

12.2Non-promotional product support, medical information, direct healthcare professional

communication (DHPC) and other non-promotional activities; pre-licence activities

12.3Codes of conduct: promotional policy and procedures; Good Promotional Practice; pre-

approval and post-approval activities; disclosure of transfers of value

12.4Advertising: claims, prescribing information, media and digital methods, audiences,

compliance, ethics, control and approval

12.5 Publication strategy for clinical trials and clinical research studies

12.6 Support of the development of clinical guidelines

12.7 Post-marketing studies

12.8 Educational meetings; sponsored meetings and sponsored publications

12.9Characterising patient preferences used in health technology assessment dossiers or research

e.g. discrete choice experiments (DCE), focus groups

12.10 Principles and practice of marketing; market structure and competition; market analysis

13.1Principles and methods of the economics of healthcare, health economics and

pharmacoeconomics

13.2 Evidence-based medicine (EBM)

13.3Health-related quality of life / patient-reported outcomes: concepts and methods of

measurement.

13.4Pricing and reimbursement strategies e.g. value-based pricing, reference pricing, risk-sharing

schemes, advance budgetary notifications

13.5 Market access, national and local formularies

13.6Measurement of healthcare efficiency: principles of international governmental policy and third-

party reimbursement

13.7Economics of industry: competition, licensing, co-marketing and life-cycle management to

include generics, biosimilars, parallel imports and switching strategies

13.8The appraisal of health-economic evidence, systematic reviews and meta-analyses, health

technology assessment

13.9Patient access to medicines: alternative funding routes for non-reimbursed products; preparing

a simple economic impact model

SECTION 12. Information, Promotion and Education

SECTION 13. Economics of Healthcare, Health Economics and Pharmacoeconomics

IMI PHARMATRAIN SYLLABUSTHE SYLLABUS FOR PHARMACEUTICAL MEDICINE / DRUG DEVELOPMENT

(V2.0; January 2018)

和訳

SECTION 1. 創薬共同研究（産学連携等）を含む研究の戦略と組織体制疾患モデル；ターゲットの認識、評価、選択受容体に基づく取り組み：ｱｺﾞﾆｽﾄ、ｱﾝﾀｺﾞﾆｽﾄ、酵素阻害剤；ｼﾞｪﾉﾐｸｽ、ﾌﾟﾛﾃｵﾐｸｽ

その他の治療ｱﾌﾟﾛｰﾁ：和漢医薬、薬剤結合型機器、先進医療 例：遺伝子治療、細胞療法、組織工学

更なる開発に向けたHitからリード、リード品目の最適化と開発候補の選択新規化合物のｲﾝ･ｼﾘｺ、ｲﾝ･ﾋﾞﾄﾛおよびｲﾝ･ﾋﾞﾎﾞでの試験ﾄﾗﾝｽﾚｰｼｮﾅﾙﾒﾃﾞｨｼﾝの基礎

動物とﾋﾄの薬理学、分子生物学、生理学的な関係　例：ﾊﾞｲｵﾏｰｶｰ、機能的ｲﾒｰｼﾞﾝｸﾞ、ﾓﾃﾞﾘﾝｸﾞ、ｼﾐｭﾚｰｼｮﾝ

SECTION 2. 医薬品開発：計画

企業および国際的なレベルでの新薬の包括的開発に必要な要素と機能

品質ﾏﾈｼﾞﾒﾝﾄ計画

ﾌﾟﾛｼﾞｪｸﾄ管理の手法：TPPとTPCから申請に至るまでの開発計画、ﾌﾟﾛｼﾞｪｸﾄﾁｰﾑ、ﾂｰﾙ、意思決定の中心的役割

特殊集団（例：高齢者、小児、希少疾患患者、禁治産者）に対するプログラムの計画

途上国における開発プログラムﾗｲｾﾝｽ・ｲﾝ/ｱｳﾄを含めたR&Dのﾎﾟｰﾄﾌｫﾘｵ計画(事業開発)

ﾘｿｰｽ計画：予算化、経費管理

医薬品開発に関する企業財務：財務管理、投資利益率、固定資産、予算、会計、収益

SECTION 3. 非臨床試験

新薬の薬理研究に対する疾患機序に関するｲﾝ･ｼﾘｺや動物・細胞モデル

小分子化合物、生物製剤、先進医療における非臨床安全性と毒性ﾊﾟｯｹｰｼﾞ面での相違点

遺伝毒性・一般毒性・ﾄｷｼｺｷﾈﾃｨｸｽによる質的量的な評価につながる動物やﾋﾄや細胞調整物でみられる化合物や代謝産物の薬理と毒性に関する類似点・相違点、

ｲﾝ･ｼﾘｺ、ｲﾝ･ﾋﾞﾄﾛとｲﾝ･ﾋﾞﾎﾞでの定性的・定量的評価の目的；急性および慢性の薬物投与における適切な検査の選択

薬物による臓器障害・機能不全に共通するﾒｶﾆｽﾞﾑ: 探索と解明;病理学的評価　例：構造的染色や

免疫組織化学;　機能的評価　例:QTcインターバル検査、肝・肺の機能検査

開発計画、薬事上の対応、臨床・非臨床薬理、目的とする臨床使用や投与経路をふまえた毒性試験のｽｹｼﾞｭｰﾙ化

毒性試験計画、ﾃﾞｰﾀﾏﾈｼﾞﾒﾝﾄ、品質保証、報告書作成の規模・費用・管理

定期的毒性レビュー、臨床試験ﾌﾟﾛﾄｺﾙや治験薬概要書への反映、被験者での発生が考えられる・実際に観察された毒性との相関

小分子・高分子化合物の過敏症を含めた安全性薬理

ﾄｷｼｺｷﾈﾃｨｸｽ；ｲﾝ･ﾋﾞﾄﾛとｲﾝ･ﾋﾞﾎﾞ試験；吸収・分布・代謝・排泄（ADME）

生物製剤、ﾜｸﾁﾝ、先進医療における非臨床試験　例：遺伝子治療、細胞療法、組織工学

ﾊﾞｲｵ医薬品製剤の非臨床試験

SECTION 4. 製剤開発

ﾊﾞｲｵ医薬品や先進医療を含めた原体と製品の製剤開発：剤型、製造と供給；ﾗﾍﾞﾙと外観；安定性と保存；純度；適合性；廃棄

経済的な新規化合物の１次製造と試験用・市販用製剤の２次製造

化合物の特性と目的とする使用法にあわせた剤型選択

後発医薬品やﾊﾞｲｵｼﾐﾗｰ製品等の後続製剤を含めた製品最終化にむけての生物学的同等性、安定性、不純物、不適合性に関するｲﾝ･ﾋﾞﾄﾛやｲﾝ･ﾋﾞﾎﾞの剤型テストの基礎

試験薬の供給計画； 試験薬の包装とﾗﾍﾞﾙ；安定性と保存条件；薬剤の分配；残薬の廃棄

試験薬供給：ﾏｯﾁﾝｸﾞ・ﾌﾟﾗｾﾎﾞや対照薬の調整薬局法：役割、使用、ﾋｴﾗﾙｷｰ

SECTION 5. 探索的開発（分子からPOCまで）

目的とする適応症、ﾊﾞｲｵﾏｰｶｰ、有効性安全性の要件やｴﾝﾄﾞﾎﾟｲﾝﾄ、臨床試験やPOC試験に進むう

えでの‘go’ ‘no-go’の意思決定.

ﾋﾄへの投薬開始前に必要とされる非臨床ﾃﾞｰﾀとﾘｽｸの評価

探索的第0相試験：探索的なﾏｲｸﾛﾄﾞｰｽﾞや治療量以下の用量での試験；ﾏｲｸﾛﾄﾞｰｽﾞの意義、限

界、適用（ICH M3)

早期臨床開発の計画：探索的開発試験：-FIHからPOCへ-ﾓﾃﾞﾘﾝｸﾞとｼﾐｭﾚｰｼｮﾝ-ﾋﾄでの忍容度、代謝、PK、PD、安全性-患者や健常人における安全性評価-用量漸増の安全性委員会（委員の要件と役割）-先進医療や薬物結合性器具に関する特別な配慮

半減期やVoD、ｸﾘｱﾗﾝｽを含めたPK、ADME、PK/PDﾓﾃﾞﾙ；革新的医薬品のPKに影響する内的外的要因；用量と蓄積、ﾊﾞｲｵｱﾍﾞｲﾗﾋﾞﾘﾃｨ、生物学的同等性、ﾎﾟﾋﾟｭﾚｰｼｮﾝPK

ﾌｧｰﾏｺｼﾞｪﾈﾃｨｸｽ/ﾌｧｰﾏｺｼﾞｪﾉﾐｸｽ

FIHや後続の第2・３相試験での用量計画や試験デザインへのPKの活用を含めた、FIH試験や

早期臨床試験における開始用量や用量漸増計画

FIH試験；患者と健常人；POCと用量設定試験の原則；POC試験のためのﾊﾞｲｵﾏｰｶｰの評価/ﾊﾞﾘ

ﾃﾞｰｼｮﾝ

目的とした効能効果、用法用量と薬物伝達概念/製剤；追加的に必要とされる動物毒性要件；再配合試験；新たな薬理試験；安全性リスクを評価し、継続開発の期間中に適用するリスクマネジメント手法の開発が可能となるようなリスク予知のアルゴリズム

SECTION 6. 検証的開発：戦略

臨床開発計画（CDP)のｵﾌﾟｼｮﾝ；資産リスクの評価と最小化；懸賞的臨床開発計画のスケジュールと意思決定ﾎﾟｲﾝﾄ

ﾀｰｹﾞｯﾄ･ﾌﾟﾛﾀﾞｸﾄ･ﾌﾟﾛﾌｧｲﾙ（TPP)から検証的臨床開発計画ﾃﾞｻﾞｲﾝへ；ピボタルその他の第3相試験；第3相臨床試験のための１次・２次ｴﾝﾄﾞﾎﾟｲﾝﾄや非博対象薬の選定；適応症の最終決定；被験者のためのﾘｽｸ最小化計画

探索的臨床試験に参加する国/地域の選定；対象被験者数と選定基準；薬物伝達ｼｽﾃﾑ；剤型；用法；試験薬供給-この段階での開発にこれらすべてが適切であると保証すること

ﾗｲｾﾝｼﾝｸﾞの前後における臨床試験プログラムの整合を含めた計画と国際協調；競合するクラスのデータや非臨床データ、既存の臨床試験データの許可範囲内での活用

ﾗｲﾌ･ｻｲｸﾙ･ﾏﾈｼﾞﾒﾝﾄの計画: 追加適応や追加剤型の取得

ﾌｨｰﾄﾞﾊﾞｯｸの入手と実行

SECTION 7. 臨床試験

非劣性/優越性/その他のﾃﾞｻﾞｲﾝ；ﾌﾟﾗｾﾎﾞ/その他の対照薬；対象となる患者集団；ｻﾝﾌﾟﾙｻｲｽﾞ；試験場所；盲検化；ｴﾝﾄﾞﾎﾟｲﾝﾄ；統計解析方法の選択などを考慮した試験ﾃﾞｻﾞｲﾝの選択

新しい試験ﾃﾞｻﾞｲﾝや必要な技術

製造販売後臨床試験；第4相臨床試験；非介入/観察研究；ﾘｱﾙﾜｰﾙﾄﾞﾃﾞｰﾀ（RWD)の創出；市

販後研究；患者団体ﾚｼﾞｽﾄﾘ

治験薬概要書：内容、ﾚﾋﾞｭｰと更新維持ﾌﾟﾛﾄｺﾙの作成と修正

臨床試験のﾌｨｰｼﾞﾋﾞﾘﾃｨの調査と試験責任医師の募集；試験前の訪問；試験医師説明会と研修会

試験施設のﾏﾈｼﾞﾒﾝﾄと施設要件の評価を含めた試験管理

試験医師やアカデミア/医療機関、CRO、SMOとの契約；出版の権利

臨床試験登録

当該試験についての意思決定　例：ｺｰﾄﾞ･ﾌﾞﾚｲｸ、中間解析、データ安全性ﾓﾆﾀﾘﾝｸﾞ委員会（DSMC)、早期終了

試験薬の取り扱いと説明責任有害事象の評価と報告；緊急時の対応ﾓﾆﾀﾘﾝｸﾞと原資料閲覧：臨床試験ﾓﾆﾀﾘﾝｸﾞの進化ﾄﾗｲｱﾙ･ﾏｽﾀｰ･ﾌｧｲﾙ (TMF)

品質のﾏﾈｼﾞﾒﾝﾄ; SOP; 品質保証と品質管理; 独立した調査; 査察

臨床試験データの報告；ﾃﾞｰﾀの共有とｵｰﾌﾟﾝﾃﾞｰﾀ、透明化、集積報告ﾚﾋﾞｭｰ、年次試験報告書

臨床試験における特殊集団への配慮　（例：高齢者、小児、極端な年齢層（未熟児、新生

児）、禁治産者、希少疾患患者）

医療機器と医薬品結合型機器の試験

SECTION 8. 倫理と法的課題

倫理：原則、ヘルシンキ宣言を含む歴史、EU Directive 2001/20/EC、倫理審査、ｲﾝﾌｫｰﾑﾄﾞ･ｺﾝｾﾝﾄ、

被験者の安全性と尊厳、ICH GCPの役割とその他のGxPs

ﾊﾞｲｵﾒﾃﾞｨｶﾙ研究と製薬医学における倫理的課題

被験者保護；特にCOIを回避するためのスポンサーと試験医師との責務

科学的な理論、統計学的頑健さ、適切な被験者集団、比較対照薬やｴﾝﾄﾞﾎﾟｲﾝﾄの選定を含めた、FIHから市販後研究・疫学研究におけるﾘｻｰﾁ･ｸｴｽﾁｮﾝや試験ﾃﾞｻﾞｲﾝにおける倫理的課題；比較臨

床研究における均衡の確保；COIの管理

ﾃﾞｰﾀﾍﾞｰｽ検索や広告を含めた被験者募集の方法に関する倫理的課題；被験者とのｺﾝﾀｸﾄ；被験者への支払い

ﾍﾞﾈﾌｨｯﾄｰﾘｽｸのﾊﾞﾗﾝｽを含めたｲﾝﾌｫｰﾑﾄﾞ･ｺﾝｾﾝﾄのﾌﾟﾛｾｽ、特殊集団（例　高齢者、小児、緊急医療、禁治産者）を含めた被験者の参加要件

ﾌﾟﾗｲﾊﾞｼｰ、秘密保持、臨床試験ﾃﾞｰﾀの保護や広報に関する合意

被験者・試験責任医師・施設の保障と保険；苦情への対応。

試験のﾌｫﾛｰｱｯﾌﾟ、試験薬の継続、承認前の活動、保険償還前の活動などに関する倫理的課題

ｹﾞﾉﾑなどの解析を目的とした試験検体に関する倫理的課題：科学的理論、倫理的かつ匿名化の結果：ﾊﾞｲｵﾊﾞﾝｸ

特殊集団（例　高齢者、小児、緊急医療、禁治産者）における臨床試験の倫理的課題

先進医療研究におけるｽﾃｰｸﾎﾙﾀﾞｰ間での倫理的課題（例　遺伝子治療、細胞療法、組織工学）

発展途上国における臨床試験の倫理的課題ﾊﾞｲｵﾒﾃﾞｨｶﾙ研究や臨床開発における虚偽と不正行為

SECTION 9. ﾃﾞｰﾀ･ﾏﾈｼﾞﾒﾝﾄと統計

試験デザインの統計学的見方

基礎；ﾗﾝﾀﾞﾑ化、ｴﾝﾄﾞﾎﾟｲﾝﾄの選択、ﾊﾞｲｱｽの回避、ﾃﾞｰﾀ欠損の回避、ｻﾝﾌﾟﾙｻｲｽﾞの算出

中間解析；有効性、無益、毒性

用量設定試験のﾃﾞｻﾞｲﾝ

同等性と非劣性の試験：理論、ﾏｰｼﾞﾝの選択

ｱﾀﾞﾌﾟﾃｨﾌﾞ･ﾃﾞｻﾞｲﾝ；優位性、懸念、統計学的かつ運用上のﾊﾞｲｱｽ回避を含む基本的考え

データマネジメント

ﾃﾞｰﾀ収集；患者日誌を含めた手動および電子的なﾃﾞｰﾀのｵﾌﾟｼｮﾝ

調査票（CRF)のﾃﾞｻﾞｲﾝと記入；原資料閲覧、ｸｴﾘ作成と解決

ﾃﾞｰﾀ処理；データ入力、有害事象のｺｰﾄﾞ化、既往歴と併用薬；ﾌﾟﾛﾄｺﾙ違反と逸脱の確認、

ﾃﾞｰﾀﾍﾞｰｽ：ﾒｲﾝﾃﾅﾝｽ、ｾｷｭﾘﾃｨ、標準化、手順の簡素化、CDISC

解析のための統計学的方法

基本：帰無仮説と対立仮説、ﾀｲﾌﾟ1とﾀｲﾌﾟ2のｴﾗｰ、p値、信頼区間、ﾊﾟﾜｰ、解析セット

ｴﾝﾄﾞﾎﾟｲﾝﾄ；ﾀｲﾌﾟ（連続、ﾊﾞｲﾅﾘｰ/ｶﾃｺﾞﾘｶﾙ、生存時間、評価ｽｹｰﾙ）、ﾃﾞｰﾀ変換、１次

と２次のｴﾝﾄﾞﾎﾟｲﾝﾄ、多重性の対応、変動の縮小

特定手法；ｼﾝﾌﾟﾙな統計解析（ﾊﾟﾗﾒﾄﾘｯｸとﾉﾝ･ﾊﾟﾗﾒﾄﾘｯｸ）、ｵｯｽﾞ比、ﾘｽｸ比、ﾊｻﾞｰﾄﾞ

比、ｶﾌﾟﾗﾝ･ﾏｲﾔｰ曲線、初期値の不均衡を矯正し、変動を縮小するためのﾓﾃﾞﾘﾝｸﾞ

均質性の評価：ﾌｫﾚｽﾄ･ﾌﾟﾛｯﾄとｻﾌﾞｸﾞﾙｰﾌﾟ評価、交互作用の解析

ﾃﾞｰﾀ補完に際しての欠損への対応

ﾍﾞｲｽﾞ統計学：基本的考え

安全性ﾃﾞｰﾀ；有害事象、検査値、その他の安全性関連データの評価に用いる図表

診断（判断）：感度、特異度、ROCｶｰﾌﾞの紹介

ﾒﾀ･ｱﾅﾘｼｽ：区別とﾌﾟｰﾘﾝｸﾞ、固定効果ﾓﾃﾞﾙとﾗﾝﾀﾞﾑ効果ﾓﾃﾞﾙ

観察研究：ﾊﾞｲｱｽを最小化するためのﾏｯﾁﾝｸﾞ

統計学的ﾌﾟﾛｾｽ

ﾌﾟﾛﾄｺﾙの統計学的解析のｾｸｼｮﾝ内容と統計解析計画

統計解析報告書の作成と臨床試験総括報告書および臨床論文への貢献；統計学的解

析に臨床的吟味を含める

論文の批判的吟味

SECTION 10. 薬事

薬事の背景と一般則；管理メカニズムの進化；行政当局間での相違

薬事的管理の原則; 国際機関（例；WHO、WMA、CIOMS、各国規制当局）からの現実的なｲﾝﾌﾟｯﾄ

日米EU医薬品規制調和国際会議 (ICH).の活動と貢献

医薬品開発に関連するGood Practiceについて（例　GMP,GLP,GCP, GPvP)

承認取得前後の薬事対応の統括; 製品戦略の企画とﾚﾋﾞｭｰ

新医薬品の評価と承認におけるEUでの薬事ﾌﾟﾛｾｽ；科学的ｱﾄﾞﾊﾞｲｽ；訴訟と仲裁の手順;

EMA承認の維持、変更、取り下げに関する手順；ﾌﾘﾌｧﾗﾙの手順；秘密保持と透明化

薬事手順；希少疾患、小児用医薬品、先進医療薬事手順；後発医薬品、ﾊﾞｲｵｼﾐﾗｰ

EU、アメリカ、その他の国々（ROW)の薬事体制と各国独自の規制要件

CTA、継続と中止に関するEUの薬事規制とｶﾞｲﾀﾞﾝｽ；EUでの単独申請ﾎﾟｰﾀﾙ；大幅なﾌﾟﾛﾄｺﾙ変

更；透明性；EU、アメリカ、日本、その他の国での臨床試験規則

ｺﾓﾝ･ﾃｸﾆｶﾙ･ﾄﾞｷｭﾒﾝﾄ (CTD & eCTD). 臨床概論、臨床総括

主要国における製造販売承認の準備と申請 (MAA, NDA, JNDA, CNDA)

製品情報に関する規制: SmPC,　添付文書, 患者情報ﾘｰﾌﾚｯﾄ

処方薬と一般薬; ｽｲｯﾁOTC

未承認薬の提供と使用に関する規制条項製品に対する制限、中止、取り下げの手順；製品欠陥とﾘｺｰﾙ医療機器に関する規制

天然物に対する規制　例　ﾊｰﾌﾞ、ｼﾝﾊﾞｲｵﾃｨｸｽ、伝統療法、漢方薬

ﾘｽｸ･ﾏﾈｼﾞﾒﾝﾄ; EUのRisk Management Plan (RMP); アメリカのRisk Evaluation and Mitigation

Strategies (REMS)、その他の承認薬に対するﾓﾆﾀﾘﾝｸﾞ　例　黒▼（EU)、黒枠警告（US)

定期的ﾍﾞﾈﾌｨｯﾄ・ﾘｽｸ評価報告（PBRER)、定期的安全性最新報告（PSUR）、治験安全性最新報告（DSUR)

医薬品への早期アクセスに関する規制と手順偽造医薬品

承認後安全性試験；承認後有効性試験；医師主導試験

SECTION 11. 医薬品の安全性、ﾌｧｰﾏｺﾋﾞｼﾞﾗﾝｽ、薬剤疫学医薬品の安全性とﾌｧｰﾏｺﾋﾞｼﾞﾗﾝｽにおける製薬専門家の役割

有害事象(AEs), 副作用(ADRs), 重篤有害事象(SAEs)、重篤未知の副作用(SUSARs)の評価と分類; 相関と因果関係のｴﾋﾞﾃﾞﾝｽ.

ﾍﾞﾈﾌｨｯﾄ･ﾘｽｸのﾊﾞﾗﾝｽの概念

臨床試験における有害事象の情報収集

承認前後の段階で遊学事象は副作用疑いを評価し報告する場合の試験責任医師、主治医、試験ﾓﾆﾀｰ、ｽﾎﾟﾝｻｰと製造業者の役割；承認前後の段階での薬事報告要件；医学文献報告

有害事象の継続と重症度、ﾘｽｸ最小化における素因と共存疾患のｲﾝﾊﾟｸﾄ

市販後の自発報告

報告可能な事象；過量投与、投薬過誤、適応外使用、誤使用と乱用、妊娠中の服薬経験

薬物相互作用薬剤疫学疫学的なﾌｧｰﾏｺﾋﾞｼﾞﾗﾝｽ情報の主な出所ｼｸﾞﾅﾙの検出、解釈、管理課題・危機管理などの承認後のﾘｽｸ･ﾏﾈｼﾞﾒﾝﾄﾘｽｸ･ｺﾐｭﾆｹｰｼｮﾝ

SECTION 12. 情報、販売促進、教育

患者と患者団体に向けた情報と開示；患者参画活動におけるｺﾝﾌﾟﾗｲｱﾝｽ

販促以外の製品ｻﾎﾟｰﾄ、医薬情報、医療関係者への直接通信（DHPC)、その他の活動；ﾗｲｾﾝｽ前の活動

行動基準; 販促方針と手順; Good Promotional Practice；承認前後の活動；金品授受の開示

宣伝活動: ﾚｾﾌﾟﾄ、処方情報、ﾒﾃﾞｨｱやﾃﾞｼﾞﾀﾙ広報、聴衆、ｺﾝﾌﾟﾗｲｱﾝｽ、倫理、管理、承認

臨床試験と臨床研究の出版戦略臨床ｶﾞｲﾄﾞﾗｲﾝの作成支援市販後試験教育研修;ｽﾎﾟﾝｻｰされた会議や論文出版.

医療技術評価の手法や研究に用いる患者嗜好性の特徴　例　離散選択実験(DCE)、ﾌｫｰｶｽｸﾞﾙｰ

ﾌﾟ

ﾏｰｹﾃｨﾝｸﾞの原則と実践；市場構造と競合；市場分析

SECTION 13. 保健医療の経済学、医療経済学、薬剤経済学

保健医療の経済学、医療経済学、薬剤経済学の原則と手法

ｴﾋﾞﾃﾞﾝｽ･ﾍﾞｰｽﾄﾞ･ﾒﾃﾞｨｼﾝ (EBM）

健康関連QOL/患者報告ｱｳﾄｶﾑ；　概念と測定方法

価格と償還の戦略　例　ﾊﾞﾘｭｰに基づく価格、参照価格、ﾘｽｸ分散方式、事前予算通知

市場ｱｸｾｽ、各国および地域の処方

医療効率の測定；国際的な国家政策と第3者償還の原則

業界の経済学:；後発医薬品、ﾊﾞｲｵｼﾐﾗｰ、並行輸入やｽｲｯﾁ戦略を含めた競合、ﾗｲｾﾝｼﾝｸﾞ、ｺ･ﾏｰｹ

ﾃｨﾝｸﾞとﾗｲﾌｻｲｸﾙﾏﾈｼﾞﾒﾝﾄ

医療経済的なｴﾋﾞﾃﾞﾝｽ、ｼｽﾃﾏﾃｨｯｸ･ﾚﾋﾞｭｰやﾒﾀ･ｱﾅﾘｼｽ、医療技術評価 のｱﾌﾟﾚｲｻﾞﾙ

患者の医薬品ｱｸｾｽ；償還対象外の製品に対する別の支払い方法；シンプルな経済ｲﾝﾊﾟｸﾄﾓﾃﾞﾙの準備